Identification and validation of CDC20 and ITCH as ubiquitination related biomarker in idiopathic pulmonary fibrosis

TL;DR

This study identifies CDC20 and ITCH as potential biomarkers in idiopathic pulmonary fibrosis, linking them to disease mechanisms like inflammation and tissue changes.

Contribution

The study introduces CDC20 and ITCH as novel ubiquitination-related biomarkers for idiopathic pulmonary fibrosis.

Findings

53 ubiquitination-related genes were identified, including 36 up-regulated and 17 down-regulated in IPF.

CDC20 and ITCH were validated as differentially expressed in IPF patients and cells.

Key genes are linked to epithelial-mesenchymal transition, inflammation, and apoptosis in IPF.

Abstract

Ubiquitination plays a crucial role in various diseases. This study aims to explore the potential ubiquitination related genes in IPF.

The gene microarray dataset GSE24206 was obtained from GEO database. Subsequently, through differential expression analysis and molecular signatures database, we obtained 1734 differentially expressed genes and 742 ubiquitination related genes. Through the venn diagram analysis, we obtained 53 differentially expressed ubiquitination related genes. Then, gene-ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interactions (PPI) and gene set enrichment analysis (GSEA) were applied for the differentially expressed ubiquitination related genes. Finally, the expression of CDC20 and ITCH in IPF patients and cells were validated by qPCR and western blot assay.

A total of 53 differentially expressed ubiquitination related genes (36 up-regulated genes and 17 down-regulated genes) were identified between 17 IPF patients and 6 healthy controls. GO and KEGG enrichment analysis of ubiquitination related genes mainly involved in regulation of protein ubiquitination, regulation of post-translational protein modification and ubiquitin mediated proteolysis. The PPI results demonstrated that these ubiquitination related genes interacted with each other. The GSEA analysis results for some of the hub genes mainly involved epithelial mesenchymal transition, inflammatory response, hypoxia, and apoptosis. The experiment expression level of CDC20 and ITCH in IPF patients and IPF cells were consistent with the bioinformatics analysis results.

We identified 53 potential ubiquitination related genes of IPF through bioinformatics analysis. CDC20 and ITCH and other ubiquitination related genes may influence the development of IPF through epithelial mesenchymal transition and inflammatory response. Our research findings provide insights into the mechanisms of fibrosis and may provide evidence for potential therapeutic targets for fibrosis.

The online version contains supplementary material available at 10.1186/s41065-025-00401-y.

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